PB2201: ASSOCIATION OF HIGH PLATELETCRIT WITH THROMBOTIC RISK IN POLYCYTHEMIA VERA DEPENDS ON HEMATOCRIT AND LEUKOCYTE COUNT
Authors: Ivan Krecak, Ivan Zekanovic, Martina Morić Perić, Hrvoje Holik, Bozena Coha, Vlatka Perisa, Marko Lucijanic
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by erythrocytosis and the presence of increased number of large and activated platelets in the circulation. While the control of hematocrit remains the cornerstone of treatment in PV, normalization of platelet counts does not seem to correlate with lower thrombotic risk. Aims: To investigate the prognostic role of plateletcrit (PCT), a measure of total circulating platelet mass, in PV patients. Methods: This was a retrospective multicenter study including JAK2-V617F-positive PV patients diagnosed according to 2016 WHO criteria. Clinical and laboratory data was recorded through medical chart review. Cardiovascular (CV) risk factors considered were arterial hypertension, hyperlipidemia, diabetes, smoking, and chronic kidney disease. Baseline PCT was calculated as mean platelet volume (MPV) x platelet count/10 000 and was expressed as a percentage (normal range 0.22-0.24%). Receiver operating characteristic curve (ROC) analysis was used for sensitivity and specificity testing. Categorical variables were compared with the chi-square test and continuous variables were compared with the Mann-Whitney U test. Thrombosis-free survival (TFS) was measured from diagnosis until an arterial/venous event or death. Survival analyses were performed using the Kaplan-Meier and the Cox-regression analysis. Results: Ninety patients were included in the study; median age was 70 years (range 21-92), 45 (50%) were females, and the median PCT was 0.45% (range 0.09-1.15%). ROC curve analysis defined the optimal value of PCT as >0.38%. Patients with higher PCT (>0.38%; n=56) were older, had higher total leukocytes, granulocytes and platelets and higher MPV (p<0.050 for all analyses), whereas the associations of higher PCT with prior thrombosis (p=0.067), presence of high-risk disease (p=0.094) and the need for hydroxyurea (p=0.077) had marginal statistical significance. Median follow-up was 43.5 months; 13 thrombotic events and 20 deaths occurred during this time. Patients presenting with higher PCT had an inferior TFS (median 96 months) when compared to those with lower PCT (median not reached, HR 2.82, p=0.010), as shown in Figure 1. Higher PCT (HR 3.87, p=0.048) and the absence of aspirin use (HR 7.84, p=0.001) remained independently associated with an inferior TFS in the multivariate Cox regression model also including sex, high-risk disease, hydroxyurea, total leukocyte count and CV risk factors (p>0.050 for all analyses). Furthermore, there were statistically significant interactions between PCT, hematocrit and TFS (p=0.001) and between PCT, leukocyte count and TFS (p=0.001). The adverse effect of higher PCT on TFS was more pronounced in patients presenting with leukocytosis (>10x109/L; HR 4.20, p=0.009) and with higher baseline median hematocrit (>54%; HR 4.46, p=0.043) than in those without leukocytosis (HR 1.56, p=0.482) or lower hematocrit (HR 2.28, p=0.094). Summary/Conclusion: This study suggests that higher baseline PCT may be associated with an increased thrombotic risk in PV. This risk seems to be moderated by baseline hematocrit and leukocyte count, with patients showing features of stronger myeloproliferation having stronger association of PCT with thrombosis or death. Considering the recent evidence suggesting suboptimal platelet inhibition in MPNs, PCT may serve as an easily obtainable tool for the comprehensive quantification of the total circulating platelet mass. Further studies are needed to clarify whether serial measurements of PCT may help to guide cytoreductive and platelet-targeted treatments in MPN patients. Limitations of this study are its retrospective design and limited number of patients included.Keywords: Thrombosis, Platelet, Myeloproliferative disorder, Myeloid malignancies